Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria

The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis

Usefulness of the assessment of discharge accumulation in the lower airways and tracheal septum thickening in the differential diagnosis of recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) in the horse

The aim of the present study was to use endoscopic evaluation to compare the grade of accumulation of discharge in the lower airways of horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD), and to estimate the usefulness of endoscopic evaluation in differential diagnosis of these diseases. Endoscopic evaluation consists of: the amount of discharge in the lower part of the trachea and tracheal bifurcation, and the assessment of tracheal septum thickness. This study was performed on 248 horses, 10 were healthy, 97 were diagnosed as RAO, and 141 were diagnosed as IAD. In all animals both a clinical and endoscopic examination were performed. During endoscopy, a score of mucus accumulation was estimated in 3/4 lower of the trachea and in the tracheal bifurcation. In addition to this, thickening of the tracheal septum was also assessed. According to the results of this study, it was estimated that the accumulation of mucus in the lower airways was much more advanced in RAO horses compared to horses with IAD. In horses with RAO there was a marked thickening of the tracheal septum compared to IAD horses. The results indicate the efficacy of scoring the amount of mucus in the tracheal lumen and tracheal bifurcation, as well as the efficacy of the assessment of tracheal septum thickness in the diagnosis of these diseases

Cytological evaluation of tracheal aspirate and broncho - alveolar lavage fluid in comparison to endoscopic assessment of lower airways in horses with recurrent airways obstruction or inflammatory airway disease

The aim of the present study was to compare the grade of discharge accumulation in the tracheal lumen, area of tracheal bifurcation, main bronchi and the tracheal septum thickness with the cytology of the tracheal aspirate (TA) and broncho-alveolar lavage fluid (BALF) in horses with recurrent airways obstruction and inflammatory airway disease from those horses. This study was conducted on 96 horses with RAO, 139 horses with IAD and 10 control horses. In all the horses, both clinical and endoscopic examinations were performed. During endoscopy, a score of mucus accumulation was estimated in 3/4 lower of the trachea and in the tracheal bifurcation. In addition, thickening of the tracheal septum was also assessed; tracheal aspirates and broncho-alveolar lavage were performed. An estimate of cell percentage was done in TA and BALF samples. In horses suffering from RAO and IAD, there was a positive correlation between the percentage of neutrophils and the accumulation of discharge, and in the IAD group, there was a negative correlation between the percentage of eosinophils and the accumulation of discharge. There was no correlation between tracheal septum thickening and the percentage of neutrophils and/or eosinophils

Serum paraoxonase 1 (PON1) activity and lipid metabolism parameters changes in different production cycle periods of Holstein - Friesian, Polish Red and Norwegian breeds

We investigated the measurement of paraoxonase 1 (PON1), as a potential marker of redox state changes in dairy cows, its involvement in lipid metabolism and compared it with superoxide dismutase (SOD) activity changes. We also evaluated lipid metabolism parameters associated with dairy production. PON1 paraoxonase and arylesterase acitvities, SOD activity, beta-hydroxybutyrate (BHB), uric acid (UA), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol and triglyceride concentrations were measured in Holstein-Friesian, Polish Red and Norwegian breeds serum in two production cycles. Our data showed a significant postpartum depletion in PON1 activity and lipoprotein and lipid products concentrations, with elevated BHB values. However, there were no significant changes in SOD activity and uric acid concentrations in Holstein-Friesian and Polish Red breeds after calving. At lactation peak there was a significant SOD activity decrease correlated with standardized PON1 activity depletion in all examined breeds. The results suggest that PON1 might be a better parameter for minimal redox state changes in serum, shortly after labour in the examined breeds

ProANP as a screening biomarker for hypertrophic cardiomyopathy in Maine coon cats

The aim of this study was to determine if atrial natriuretic peptide can be used as an early screening tool for hypertrophic cardiomyopathy in Maine coon cats. Animals: The study was performed in 43 Maine coon cats of both sexes, aged 11 to 92 months. Clinical and echocardiographic examinations were done and proANP serum concentrations were measured every three months over a period of one year (each cat had a total of five examinations). Cats were divided into 3 groups based on echocardiographic results: group 1 – healthy cats, group 2 – cats with unequivocal hypertrophic cardiomyopathy results, group 3 – cats with HCM. The study showed that the concentration of atrial natriuretic peptide correlates with the severity of HCM. A significant increase in serum concentration of this peptide was observed in cats from group 3, but it did not differ significantly between cats from group 2 and the healthy animals (p>0.05). A correlation was also found between proANP and age of the cats (p<0.01, r=0.5578) as well as between the ejection fraction (p=0.0285, r=0.5305) and end-systolic left ventricular diameter (p=0.05, r=0.48) in the affected animals. Atrial natriuretic peptide may be used to help in the diagnosis of advanced stages of HCM in Maine coon cats. Cats with high levels of proANP should be assigned to echocardiographic studies to confirm the disease

Usefulness of clinical, histopathological and some biochemical and mineral investigations in diagnosis of bovine hyperkeratosis in dairy cattle

Bovine hyperkeratosis is a polyetiologic disease that is increasingly widespread at high milk yielding dairy farms. Clinical manifestation is characterized by focal skin lesions with distinct borders. A clinical study and observation were carried out on 26 Holstein-Friesian dairy cows. During the initial phase of the condition, the skin of the affected cows was itchy, hence the animals tended to lick the skin lesions, or else rub against surrounding objects, with the resultant formation of single spots of raised coat and skin flaking resembling dandruff. These changes appeared on the posterolateral upper sides of the pelvic limbs and around the vulva. Distinct thickening of the wrinkled skin was observed as a result of excessive growth of the epidermis. The superficial part of the skin on major portions of the lesions was dry, corrugated and covered with numerous scales. The epidermis was dry, thickened and rough, with cracks showing the reddened dermal layer. When touched, the animals reacted as if in pain. The disease generally progressed into a chronic condition. In the studied cases, histopathological examination confirmed hyperkeratosis with widened hair follicle infundibulums filled with keratin, the swelling of sweat glands, epithelial atrophy of sweat glands, infiltration of inflammatory cells between and around blood vessels, and massive expansion of keratinized layers of the epidermis. The content of both calcium and magnesium as well as copper, zinc, iron and manganese in grain, roughage, mineral mixtures and in other feeds met the requirements of dairy cows. Blood biochemistry profiles revealed only slightly lower serum calcium values, while zinc values were within the reference range. However, the zinc concentration in skeletal muscles and in the skin was reduced. The mean serum alkaline phosphatase (ALP) activity in the tested animals was also somewhat decreased. Adverse environmental factors such as direct skin contact with faeces and urine as well as zinc deficiency in the cows’ tissues were significant factors in the formation of skin lesions characteristic for hyperkeratosis.Hiperkeratoza bydła jest chorobą polietiologiczną, występującą coraz częściej w gospodarstwach bydła mlecznego o wysokiej wydajności. Objawy kliniczne zlokalizowane na skórze mają ograniczony charakter. Badania i obserwacje przeprowadzono na 26 krowach mlecznych, rasy czarno-białej Na początku rozwoju choroby zaobserwowano świąd, intensywne oblizywanie się i lekkie łzawienie oraz ocieranie o otaczające przedmioty, co powodowało powstawanie pojedynczych ognisk nastroszenia sierści oraz łuszczenia się naskórka, przypominającego łupież. Zmiany pojawiały się na tylnogórnej stronie kończyn miednicznych i wokół sromu. W wyniku nadmiernego rozrostu naskórka rogowego obserwowano wyraźne zgrubienie pomarszczonej skóry. Skóra na znacznej powierzchni ogniska była sucha, pofałdowana, pokryta licznymi łuskami. Naskórek był suchy, zgrubiały, szorstki, popękany aż do widocznej czerwono zabarwionej skóry właściwej. Podczas dotyku zwierzęta odczuwały bolesność. Przebieg choroby miał charakter przewlekły. Badaniem histopatologicznym potwierdzono hiperkeratozę. Zaobserwowano poszerzone lejki mieszków włosowych wypełnionych keratyną, poszerzenie gruczołów potowych, zanik nabłonka gruczołów potowych, naciek komórek zapalnych między naczyniami krwionośnymi, naciek komórek zapalnych wokół naczyń krwionośnych oraz masywne poszerzenie warstwy rogowaciejącej naskórka. Zawartość zarówno wapnia i magnezu oraz miedzi, cynku, żelaza i manganu w granulowanej paszy treściwej oraz w mieszance mineralnej, jak i w pozostałych paszach stosowanych w żywieniu krów pokrywała ich zapotrzebowanie. Jednak wyniki badań biochemicznych wykazały, że stężenie wapnia w surowicy krów było zaniżone, zaś cynku mieściło się w granicach wartości referencyjnych. Natomiast stężenie cynku w mięśniach szkieletowych i w skórze było obniżone. Średnia aktywność ALP w surowicy badanych krów była także dość niska. Niekorzystne czynniki środowiskowe (kontakt bezpośredni skóry z kałem i moczem) oraz niedobór cynku w tkankach krów stanowiły istotną przyczynę powstawania zmian chorobowych skóry, charakterystycznych dla hiperkeratozy